CN101679175A - A process for the preparation of 1,4-dialkyl-2,3-diol-1,4-butanedione - Google Patents

A process for the preparation of 1,4-dialkyl-2,3-diol-1,4-butanedione Download PDF

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CN101679175A
CN101679175A CN200880017178A CN200880017178A CN101679175A CN 101679175 A CN101679175 A CN 101679175A CN 200880017178 A CN200880017178 A CN 200880017178A CN 200880017178 A CN200880017178 A CN 200880017178A CN 101679175 A CN101679175 A CN 101679175A
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general formula
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acid
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CN101679175B (en
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奥利维尔·安德雷
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Firmenich SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/17—Saturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Furan Compounds (AREA)

Abstract

The present invention relates to a process for the preparation of compounds of a l,4-dialkyl-2,3-diol-l,4-butanedione by a acidic aldol condensation between an alkyl glyoxal and an a-hydroxy ketone.

Description

Preparation 1,4-dialkyl group-2,3-glycol-1, the method for 4-dimethyl diketone
Technical field
The present invention relates to the organic synthesis field, more particularly relate to a kind of according to scheme (1), prepare the method for the compound of general formula (I) by the aldol condensation between alkyl glyoxal (II) and the keto-alcohol derivative (III), said condensation promotes by specific acidic conditions:
Scheme 1: according to the aldol condensation of oxalic dialdehyde of the present invention with keto-alcohol
Figure G200880017178XD00011
R wherein 1Represent straight or branched C 1-C 5Alkyl.
Background technology
The compound of following defined general formula (I) can be used as parent material and constructs the compound with more complicated skeleton, and as 4-hydroxyl-2,5-dimethyl-3 (2H)-furanone (is called as
Figure G200880017178XD00012
The trade mark of Firmenich SA).
Reported the method for the compound of various preparation general formulas (I), for example people such as Briggs is at J.Chem.Soc.Perkin.Trans.I, and 1985, what relate in 795 synthesizes 3 by the initial multistep of tartrate, 4-dihydroxy-hexane-2, and people such as 5-diketone or Bassignani are at J.Org.Chem., 1978 43, what relate in 4245 passes through with poisonous and expensive KClO 3/ OsO 42 of system oxidation costliness, the 5-dimethyl furan synthesizes 3,4-dihydroxy-hexane-2,5-diketone.The method of the synthetic compound of another report (I) be by the whole bag of tricks promote oxalic dialdehyde the reductibility dimerization reaction (for example referring to people's such as B ü chi J.Org.Chem., 1973, 38, 123).
People such as F.Naef (WO 2006/048795) have reported the preparation method by the aldol condensation between alkyl glyoxal and the keto-alcohol derivative recently again, and described method needs the pressure of special catalyst to exist, as Zn (AcO) 2Institute's reported method has quite low productive rate and the metal-salt mandatory use as catalyzer, and the unusual problem in long reaction times.
Above-mentioned preparation method is very long and expensive usually, or needs the application of heavy metal, this means the issues of purification of the finished product and the problem of waste treatment.And normal yield is very low.
Therefore, still need a kind of preparation method, it is environmental friendliness, more direct or fast and good productive rate is provided more.
Summary of the invention
In order to overcome the problems referred to above, and the optional method that the compound of preparation general formula (I) can also be provided, the present invention relates to the method that purpose is one-step synthesis compound (I) and has good yield.
Method of the present invention relates more specifically to alkyl glyoxal (II) and the aldol condensation of keto-alcohol derivative (III) under acidic conditions, does not need the pressure of metal-salt to exist, and this aldol process with technology formerly is opposite.
Therefore, method of the present invention relates to the preparation of the compound of general formula (I),
Figure G200880017178XD00021
Each R wherein 1Simultaneously or represent straight or branched C independently of one another 1-C 5Alkyl,
Described method is undertaken by the oxalic dialdehyde of general formula (II) and the aldol condensation between the alpha-alcohol ketone of general formula (III) in aqueous reaction medium,
Figure G200880017178XD00031
R wherein 1Have the implication identical with above-mentioned definition,
Figure G200880017178XD00032
R wherein 1Have the implication identical with above-mentioned definition,
Described method is characterised in that the pH of described aqueous reaction medium between 0～6, and described method is carried out to the temperature between the reflux temperature at 50 ℃.
Therefore method of the present invention does not need metal catalyst, can carry out under the situation of described compound in the presence of not.Especially, do not need the general formula FeX described in the WO 2006/048795 3Or MX 2Catalyzer, wherein M is Zn 2+, Mg 2+, Cu 2+, Fe 2+Or Ca 2+, and X is C 1-C 7Carboxylicesters, halogenide or general formula [R 2COCHCOR 2] -The acetylacetonate derivative, R 2Represent C 1-C 3Alkyl or phenyl.According to special embodiment of the present invention, described method also can need not the formula M (X) of any consumption nCatalyzer, wherein n is 2 or 3, X as defined above, and M is transition metal or alkaline-earth metal.
As mentioned above, present method is at the aqueous reaction medium of specific pH scope, and for example slightly acidic takes place to the strongly-acid medium.
According to embodiment of the present invention, present method is preferably at pH 0～4.6, and is preferred 0.0～3.0, or even 0.5～2.3 reaction medium in carry out.
Can set pH to expected value by interpolation acid or alkali in reaction medium, like this, in a single day the pH of medium sets, and during reaction can change in the scope of expectation.Also can use the mixture of acid.Optionally, can in the whole process of reaction, control and keep the pH of medium by using damping fluid.
Mention that at this following content also is useful, be tart promptly by water and compound (II) and the aqueous reaction medium itself that (III) constitutes, thereby can add acid in some cases and come the acidifying aqueous reaction medium, improve pH to expected value but need to add alkali.
Can use the acid of any kind, for example organic acid, mineral acid or acidic resins.Described acid is that those skilled in the art are known.As representative instance, can quote following acid: HCl, H 2SO 4, H 3PO 4, C 1-C 7Sulfonic acid is (as MeC 6H 4SO 3H, MeSO 3H, CF 3SO 3H), C 1-C 7Carboxylic acid is (as C 6H 5COOH, CH 3COCOOH, CH 3COOH, C 2H 5COOH) and acidic resins, (trade mark is as is known as the carboxylic acid supported on methacrylic acid group or styryl matrix or sulfonic acid
Figure G200880017178XD00041
50 * 8 or
Figure G200880017178XD00042
The resin of ICR50).
According to special embodiment of the present invention, described acid is above-mentioned carboxylic acid derivative.
Alkali as being used to regulate pH or forming damping fluid can use alkaline hydrated oxide usually, as NaOH or KOH, or basic carbonate or supercarbonate, as Na 2CO 3Or NaHCO 3
For the sake of clarity, " aqueous reaction medium " is reflected at the medium that wherein takes place in this expression.Therefore, aqueous reaction medium comprises following substances, or preferably is made up of following substances:
The complete miscible solvent of-water and non-imposed selection,
At least a acid of-appropriate amount or alkali or its mixture are as damping fluid;
The compound of the general formula (I) of-general formula (II) and compound (III) and non-imposed selection.
According to special embodiment of the present invention, described aqueous reaction medium can comprise at least 10% water, preferred at least 15% and even more preferably 20%～60% water, percentage ratio is the weight with respect to himself.Above-mentioned complete miscible solvent can exist with 0%～100% amount, and percentage ratio is the weight with respect to water.The representative instance of described solvent is tetrahydrofuran (THF) (THF), or lower alcohol, as methyl alcohol, ethanol or propyl alcohol.
According to special embodiment of the present invention, all R 1Has identical implication.According to another embodiment, all R 1Represent methylidene, so oxalic dialdehyde (II) is methyl-glyoxal, keto-alcohol (III) is hydroxyacetone (that is, 1-hydroxyl-2-acetone), and dihydroxyl diketone (I) is 3,4-dihydroxy-hexane-2,5-diketone.
With respect to oxalic dialdehyde, the consumption of keto-alcohol derivative (III) is generally 0.5～20 molar equivalent in the present invention.According to special embodiment, with respect to oxalic dialdehyde, described amount can be 2～10 molar equivalents.
The temperature that can implement the inventive method is 50 ℃～120 ℃, more preferably 65 ℃～95 ℃.If necessary, reaction can also be carried out adding to depress, so that be reflected at than carrying out under the higher temperature of described scope.
As mentioned above, the compound of general formula (I) can be the valuable intermediate that is used to prepare furanone derivatives, and is special, works as R 1And R 2When all being methyl, be used to prepare food flavouring composition 4-hydroxyl-2,5-dimethyl-3 (2H)-furanone.
Therefore, another object of the present invention is the method for the furanone of a kind of preparation general formula (IV),
Figure G200880017178XD00051
Comprise the following step:
-prepare the above compound (I) of definition according to method of the present invention; With
-make described compound (I) cyclization.
Cyclization step can be implemented according to the known method of any those skilled in the art.For example, can quote a kind of cyclization method in the presence of damping fluid, as people's such as Buchi J.Org.Chem, 1973,123 or people's such as people's such as Selinov US2002/0111500 or Briggs J.Chem.Soc.Perkin Trans.1,1985,795.
Embodiment
Embodiment
The present invention now further describes by following embodiment, and wherein temperature refers to degree centigrade, and abbreviation has the common implication in this area.
Embodiment 1
Testing sequence
70 ℃ stir down the 43wt% methyl-glyoxal aqueous solution (2.00g, 11.9mmol), pyruvic alcohol (4.42g, 59.7mmol) and acetate (1.43g, 23.8mmol) solution 16 hours (pH of reaction medium is about 2.0) of (0.9ml) in water.Last in reaction, the concentrating under reduced pressure reaction mixture, it is thick 3 to obtain 2.1g, 4-dihydroxy-hexane-2,5-diketone (is 56% by internal mark method determination purity with GC).Underpressure distillation is thick 3,4-dihydroxy-hexane-2, and the 5-diketone obtains light yellow solid 3,4-dihydroxy-hexane-2,5-diketone (1.56g, purity 74%, productive rate 66%).People such as product that obtains and B ü chi are at J.Org.Chem., and 1973, 38, described in 123 1H-NMR spectrum unanimity.
According to above-mentioned identical testing sequence, carry out the experiment of the present invention of some other foundations.In table 1, the result is summarized.
Table 1: the aldol condensation between methyl-glyoxal and the keto-alcohol obtains 3,4-dihydroxy-hexane-2,5-diketone
??N° Oxalic dialdehyde (mmol) Keto-alcohol (m.e.) 1) Solvent (ml) Acid (m.e.) 1) ??pH ??T ??(℃) Time (h) Productive rate
??1 ??11.9 ??3 Do not have Phosphate buffered saline buffer ??5.5 ??70 ??6 ??32％
??2 ??11.9 ??3 Do not have Phosphate buffered saline buffer ??4.2 ??70 ??6 ??49％
??3 ??1.2 ??5 Do not have ??CH 3COCO 2H ??2.2 ??100 ??5 ??30％
??4 ??6.0 ??5 Do not have ??CH 3COCO 2H ??2.2 ??100 ??16 ??56％
??5 ??119 ??3 ??H 2O ??(30) ??NaOH ??5.2 ??100 ??6 ??10％
??6 ??5.6 ??3 ??H 2O ??(1) ??H 3PO 4(0.05) ??0.8 ??100 ??6 ??28％
??7 ??5.6 ??3 ??H 2O ??(1) ??HCl(0.05) ??0.8 ??100 ??6 ??42％
??8 ??5.6 ??3 ??H 2O ??(1) ??H 2SO 4(0.05) ??0.8 ??100 ??6 ??41％
??9 ??5.6 ??3 ??H 2O ??(1) ??Dowex?50×8 ??2.1 ??100 ??6 ??45％
??10 ??66.6 ??3 ??H 2O ??(120) ??AcOH(3) ??1.9 ??100 ??6 ??57％
??11 ??11.9 ??3 ??H 2O ??(2.5) ??AcOH(3) ??1.9 ??70 ??16 ??64％
??12 2) ??50 ??2.5 ??H 2O ??(20) ??5.8 ??20 ??72 ??20％
??13 3) ??50 ??2.0 ??H 2O ??(30) ??3.5 ??40 ??90 ??12％
The m.e.=molar equivalent;
1) is used to set acid or the damping fluid of the pH of reaction medium, with respect to the amount of methyl-glyoxal
2) at the Zn of 0.08 molar equivalent (acac) 2There is the comparative example that carries out down (according to the embodiment among the WO 20,06/,048,795 1, table 1, N ° 2)
3) at the Zn of 0.10 molar equivalent (acetate) 2Have the comparative example who carries out down, the acid of using is AcOH, (according to WO 2006/048795 described test conditions)

Claims (9)

1. method for preparing the compound of general formula (I),
Figure A2008800171780002C1
Each R wherein 1Simultaneously or represent straight or branched C independently of one another 1-C 5Alkyl,
Described method is undertaken by the oxalic dialdehyde of general formula (II) and the aldol condensation between the alpha-alcohol ketone of general formula (III) in aqueous reaction medium,
Figure A2008800171780002C2
R wherein 1Have the implication identical with above-mentioned definition,
Figure A2008800171780002C3
R wherein 1Have the implication identical with above-mentioned definition,
Described method is characterised in that the pH of described aqueous reaction medium between 0～6, and described method is carried out to the temperature between the reflux temperature at 50 ℃; Condition is not comprise having general formula FeX 3Or MX 2The situation of catalyzer, wherein M is Zn 2+, Mg 2+, Cu 2+, Fe 2+Or Ca 2+, and X is C 1-C 7Carboxylicesters, halogenide or general formula [R 2COCHCOR 2] -The acetylacetonate derivative, R 2Represent C 1-C 3Alkyl or phenyl.
2. according to the method for claim 1, be characterised in that the formula M (X) that need not any consumption nCatalyzer, wherein n is 2 or 3, X such as claim 1 definition, and M is transition metal or alkaline-earth metal.
3. according to the method for claim 1 or 2, the pH that is characterised in that described aqueous reaction medium is 0～4.6.
4. according to each method in the claim 1～4, be characterised in that described method carries out under 65 ℃～95 ℃ temperature.
5. according to each method in the claim 1～4, be characterised in that the pH of described aqueous reaction medium comprises at least a acid or alkali or its mixture of appropriate amount, to regulate pH.
6. according to the method for claim 5, be characterised in that described acid is HCl, H 2SO 4, H 3PO 4, C 1-C 7Sulfonic acid is (as MeC 6H 4SO 3H, MeSO 3H, CF 3SO 3H), C 1-C 7Carboxylic acid is (as C 6H 5COOH, CH 3COCOOH, CH 3COOH, C 2H 5COOH) and carboxylic acid resin or sulfonate resin.
7. according to the method for claim 5 or 6, be characterised in that described alkali is alkaline hydrated oxide or basic carbonate or supercarbonate.
8. according to each method in the claim 1～7, be characterised in that each R 1Represent methylidenes all.
9. method for preparing the furanone of general formula (IV),
Comprise the following step:
-prepare each defined compound (I) in the claim 1～8 according to each method in the claim 1～8; With
-make described compound (I) cyclization.
CN200880017178.XA 2007-05-24 2008-04-30 A process for the preparation of 1,4-dialkyl-2,3-diol-1,4-butanedione Active CN101679175B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110511129A (en) * 2019-08-02 2019-11-29 厦门欧米克生物科技有限公司 A kind of method that organic amine salt catalyzes and synthesizes 3,4- dihydroxy -2,5- acetyl butyryl
CN110845313A (en) * 2019-09-27 2020-02-28 厦门欧米克生物科技有限公司 Continuous preparation method of 3, 4-dihydroxy-2, 5-hexanedione

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* Cited by examiner, † Cited by third party
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CH476658A (en) 1967-06-16 1969-08-15 Firmenich & Cie Process for the preparation of a dihydroxy-diketone
DE3837954A1 (en) 1988-11-09 1990-05-10 Basf Ag PROCESS FOR THE PREPARATION OF DIHYDROXYDIONES
CN101048359B (en) 2004-11-02 2010-06-02 弗门尼舍有限公司 Method for preparing 1,4- dialkyl-2,3- glycol-1,4-butanedione

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110511129A (en) * 2019-08-02 2019-11-29 厦门欧米克生物科技有限公司 A kind of method that organic amine salt catalyzes and synthesizes 3,4- dihydroxy -2,5- acetyl butyryl
CN110511129B (en) * 2019-08-02 2022-07-29 厦门欧米克生物科技有限公司 Method for synthesizing 3, 4-dihydroxy-2, 5-hexanedione by organic amine salt catalysis
CN110845313A (en) * 2019-09-27 2020-02-28 厦门欧米克生物科技有限公司 Continuous preparation method of 3, 4-dihydroxy-2, 5-hexanedione

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JP2010527991A (en) 2010-08-19
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